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“They thought that the Titanic was unsinkable. They thought she would last forever.
That’s what some people think about antibiotics”.

Case:

Richard (not his real name), a 72 year old man with metastatic hepatocellular carcinoma, congestive cardiac failure (ejection fraction 14%) and chronic renal impairment was admitted to hospital with possible aspiration pneumonia. Intravenous levofloxacin and clindamycin were commenced. By the 7th day of admission his respiratory status had improved somewhat but he developed diarrhea (six liquid stools in one night).

On the 10th day of admission, his respiratory status had worsened again and a portable radiograph showed new infiltrate. Since extension of his pneumonia could not be distinguished from pulmonary edema resulting from his congestive cardiac failure, the patient was treated with diuretics plus antibiotics (piperacillin/tazobactam). The microbiology laboratory called to say that his C. difficile toxin was positive and that his rectal swab for vancomycin resistant enterococci (VRE) was positive.

By the 16th day of admission, the patient’s condition was clearly deteriorating. Despite supplemental oxygen his oxygen saturation was 84%. He was somnolent and would rouse only to painful stimuli. His BUN had risen to 104. The treating team discussed transfer to the intensive care unit for mechanical ventilation and dialysis. However they noted an advance directive written four months ago, in which the patient stated that he did not wish to undergo mechanical ventilation. Upon discussion with his wife and daughter they frankly noted that his quality of life had been extremely poor and that they did not feel that further aggressive intervention was what Richard would really want. The patient continued on levofloxacin, piperacillin/tazobactam, clindamycin and metronidazole until his death 20 days after hospital admission.

Discussion

Richard’s case raises two questions for discussion. Both relate to antibiotic use.

Clostridium difficile diarrhea

Fecal incontinence due to C. difficile is a miserable experience for the dying patient and their care-givers. Other adverse consequences of C. difficile infection include dehydration, prolonged hospital stay and even toxic megacolon and death. Prior antibiotic exposure is seen in >99% of patients who develop C. difficile related diarrhea. Curtailing unnecessary antibiotic use is the major way in which occurrence of C. difficile can be reduced.

Commonly implicated antibiotics in outbreaks of C. difficile include clindamycin and advanced generation cephalosporins. Increasingly, quinolones (such as levofloxacin) are also found to be associated with C. difficile diarrhea.

In view of the frequent association between clindamycin and C. difficile, clindamycin should no longer be used as a first-line treatment in our hospitals. Metronidazole is usually a good option where an antibiotic with anti-anaerobic activity is required. In some cases of head and neck infection, coverage equivalent to that provided by clindamycin can be by way of ampicillin/sulbactam or ampicillin plus metronidazole.

Quinolones should be reserved for a few specific indications (for example, ventilator-associated pneumonia where a resistant Gram negative bacillus is likely to be implicated, chronic prostatitis, malignant otitis externa). It is not appropriate to use quinolones to “treat” organisms in the urine on the basis of a microbiology report, in the absence of symptoms and without a urinalysis indicating significant pyuria. First line therapy for community-acquired pneumonia is a macrolide and cefuroxime not levofloxacin.

Is antibiotic use appropriate for the dying patient in whom many other components of treatment have been withdrawn or withheld?

C. difficile related diarrhea is just one of the adverse consequences of antibiotic use. A frequently overlooked adverse consequence of antibiotic use is the development of antibiotic resistance. It is well known that many more patients are colonized with antibiotic resistant organisms (such as VRE) than those who are actually infected with them. Colonized patients represent a source of organisms that can be passed from patient to patient. Terminally ill patients with high nursing care requirements represent a high risk for the transmission of antibiotic resistant organisms via the hands of their caregivers.

The ethics of the choice between the interests of present terminally ill patients and the interests of future patients who perhaps have a better prognosis has been recently discussed (Marcus 2001). In patients where antibiotic therapy offers no clinical benefit, and other therapies have been withdrawn or withheld, the balance between advantages and disadvantages of antibiotic therapy is influenced heavily by the “public health” benefit of limiting antibiotic use and avoiding development of a pool of antibiotic resistance. An exception would be use of antibiotics to resolve an infection that is causing painful or distressing symptoms.

Antibiotics are a limited resource. Please use them wisely.

References:
1. Marcus EL, Clarfield AM, Moses AE. Ethical issues relating to the use of antimicrobial therapy in older patients. Clinical Infectious Diseases 2001;33:1697-1705.